Mann C J, Anderson T A, Read J, Chester S A, Harrison G B, Köchl S, Ritchie P J, Bradbury P, Hussain F S, Amey J, Vanloo B, Rosseneu M, Infante R, Hancock J M, Levitt D G, Banaszak L J, Scott J, Shoulders C C
MRC Molecular Medicine Group, Imperial College School of Medicine, London W12 ONN, UK.
J Mol Biol. 1999 Jan 8;285(1):391-408. doi: 10.1006/jmbi.1998.2298.
The assembly of atherogenic lipoproteins requires the formation in the endoplasmic reticulum of a complex between apolipoprotein (apo)B, a microsomal triglyceride transfer protein (MTP) and protein disulphide isomerase (PDI). Here we show by molecular modelling and mutagenesis that the globular amino-terminal regions of apoB and MTP are closely related in structure to the ancient egg yolk storage protein, vitellogenin (VTG). In the MTP complex, conserved structural motifs that form the reciprocal homodimerization interfaces in VTG are re-utilized by MTP to form a stable heterodimer with PDI, which anchors MTP at the site of apoB translocation, and to associate with apoB and initiate lipid transfer. The structural and functional evolution of the VTGs provides a unifying scheme for the invertebrate origins of the major vertebrate lipid transport system.
致动脉粥样硬化脂蛋白的组装需要在内质网中形成载脂蛋白（apo）B、微粒体甘油三酯转移蛋白（MTP）和蛋白质二硫键异构酶（PDI）之间的复合物。在此，我们通过分子建模和诱变表明，apoB和MTP的球状氨基末端区域在结构上与古老的卵黄储存蛋白卵黄生成素（VTG）密切相关。在MTP复合物中，形成VTG中相互同源二聚化界面的保守结构基序被MTP重新利用，以与PDI形成稳定的异二聚体，PDI将MTP锚定在apoB易位位点，并与apoB结合并启动脂质转移。VTG的结构和功能进化为主要脊椎动物脂质运输系统的无脊椎动物起源提供了一个统一的方案。
